chr3-151182072-A-G

Variant names:

• chr3-151182072-A-G
• rs10513385
• NM_001393769.1:c.1495-3258A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393769.1(MED12L):​c.1495-3258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 152,184 control chromosomes in the GnomAD database, including 955 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.074 (955 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 2 publications found

Genes affected

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

MED12L Gene-Disease associations (from GenCC):

• Nizon-Isidor syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393769.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED12L	NM_001393769.1	MANE Select	c.1495-3258A>G		intron	N/A	NP_001380698.1
	MED12L	NM_053002.6		c.1495-3258A>G		intron	N/A	NP_443728.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED12L	ENST00000687756.1	MANE Select	c.1495-3258A>G		intron	N/A	ENSP00000508695.1
	MED12L	ENST00000474524.5	TSL:1	c.1495-3258A>G		intron	N/A	ENSP00000417235.1
	MED12L	ENST00000273432.8	TSL:2	c.1075-3258A>G		intron	N/A	ENSP00000273432.4

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 11244 AN: 152066 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0740 AC: 11257 AN: 152184 Hom.: 955 Cov.: 32 AF XY: 0.0740 AC XY: 5506 AN XY: 74404

African (AFR) AF: 0.196 AC: 8115 AN: 41476

American (AMR) AF: 0.0519 AC: 794 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1041 AN: 5166

South Asian (SAS) AF: 0.0384 AC: 185 AN: 4822

European-Finnish (FIN) AF: 0.00641 AC: 68 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 834 AN: 68016

Other (OTH) AF: 0.0597 AC: 126 AN: 2112

Alfa AF: 0.0520 Hom.: 74

Bravo AF: 0.0839

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.74
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10513385; hg19: chr3-150899859;